Zambia's population of 10.2 million persons is among the world's poorest and most severely affected by HIV. The University of Alabama at Birmingham-affiliated Centre for Infectious Disease Research in Zambia (CIDRZ) is a key partner to the Zambian government in its response to the HIV epidemic through our (1) locally-relevant prevention and treatment research, (2) major support to the public sector for provision of prevention of mother-to-child HIV transmission (PMTCT) and HIV treatment services, and (3) sustained investment, through training and education, in development of local capacity to perform research and serve the public health. In this application, we propose an HIV/AIDS Clinical Trials Unit (CTU) comprising 6 Clinical Research Sites (CRSs) in Lusaka. Five of these CRSs will be co-located within primary healthcare facilities of the Lusaka District; all five have ongoing DAIDS-sponsored clinical trials in prevention, microbicides, or treatment. The 6th site will be located at the University Teaching Hospital, home to Zambia's most promising scientists and its only medical school. Throughout Lusaka, and at each of the proposed CRSs, CIDRZ supported programs are currently providing free services for PMTCT and antiretroviral therapy (ART). UAB, with support from NIAID and others, has created substantial clinical research space at each CRS that will be dedicated to CTU activities. We are proposing affiliation with 4 network leadership groups: ACTG, IMPAACT, HPTN, and MTN. Each of these networks has listed CIDRZ in its leadership group application as a preferred affiliated site. We have experience with DAIDS-sponsored clinical trials in each of the scientific areas represented by these networks in the form of completed (HPTN 024) and ongoing trials (HPTN 055, 039, 035; ACTG 5208.) We are pleased to report that the IMPAACT network ranked CIDRZ as its #1 affiliated site in its leadership group application after a competitive review of potential applicant CTUs. In the previous DAIDS funding cycle, CIDRZ focused on developing local capacity to conduct multi-center research through infrastructure investment and training of operations staff within the HPTN. In this second funding cycle, we aim to build upon our successes in Good Clinical and Laboratory Practice by developing sound Zambian scientific leadership. Toward that end, we propose a Zambian scientist as local network leader to spearhead our affiliation with each of the 4 network leadership groups. These local PIs will be paired with senior UAB and Vanderbilt scientists to assist them in their leadership role and nurture their professional development. Our long-term objective is to discover and implement HIV prevention and treatment strategies that will bring meaningful reductions in the HIV disease burden to the people of Zambia through a genuine Zambian-American collaboration. This CTU application is submitted in pursuit of this objective.